The Melanoma Antigen Gene As a Surveillance Marker for the Detection of Circulating Tumor Cells in Patients with Breast Carcinoma

Background: Circulating occult tumors cells could be used for the surveillance of metastases after primary breast carcinoma therapy, but their detection is limited by the lack of specific molecular markers. Melanoma antigen genes (MAGEs), which are expressed in malignant tissues but not in normal tissues (except for placenta and testis), might provide such a marker. To date, however, the use of MAGEs in the detection of occult tumor cells using reverse transcription-polymerase chain reaction (RT-PCR) has been limited because of the heterogeneity and low expression of individual MAGEs in tumor tissues.

Methods: We developed multiple MAGE-recognizing primers (MMRPs) that were capable of binding to the cyclic DNA of 6 MAGE-A gene subtypes (MAGE-A1-MAGE-A6). We assessed the ability of the MMRPs to detect the expression of MAGE-A gene subtypes in peripheral blood obtained from patients with benign or malignant breast disease.

Results: MAGE-A gene expression was not detected in 32 patients with benign disease but was detected in 1 of 31 patients (3%) patients with negative lymph node breast carcinoma, in 10 of 52 patients (19%) with 1-3 positive lymph nodes, in 11 of 53 patients (21%) with > or = 4 positive lymph nodes, and in 20 of 52 patients (39%) with metastatic disease. The results were statistically significant (P < 0.0001; chi-square test for linear-by-linear association). The results also showed that the detection of MAGE-A gene expression in the blood predicted tumor progression or recurrence.

Conclusions: The results suggested that MAGE-A gene expression may be used for the surveillance of circulating breast carcinoma cells after primary therapy by RT-nested PCR using MMRPs.